Work performed by our group during the last two years has led to the identification of a murine tumor cell line (L-A9) with an unusually high rate of sister chromatid exchange (SCE). We propose to use these cells together with rodent and human diploid cells with a normal rate of SCE and the cells from patients with Bloom's syndrome (BS) to investigate the biology of SCE by complementation analysis with somatic cell hybrids. Preliminary results so far obtained have shown that the high rate of SCE, typical of BS chromosomes, is fully corrected in somatic cell hybrids derived from the fusion of BS cells with Chinese hamster cells (CHO-YH21), as well as with the above mentioned L-A9 cells. Conversely the high rate of SCE of the latter murine cells is corrected in rodent human hybrids which have retained a large number of murine chromosomes, independent of the type of human parental cell type used in the fusion (normal lymphoblasts or Bloom's fibroblasts). This correction seems to be correlated with the retention of a human C-autosome. We intend now to continue and implement these studies with respect to the following main targets of investigation: (1) to use the cell hybrid model for the screening of possible genetic heterogeneity among different BS patients; (2) to establish whether or not the complementing effect for SCE of one parental genome over the other is chromosome-specific; (3) to investigate the effect of well known inducers of SCE on given types of parental cells and in hybrids between them. We are confident that these types of studies will contribute critical data on the identification and mapping of mammalian genes involved in the SCE phenomenon and, hopefully, on the pathogenesis of Bloom's syndrome and its association with tumor malignancy.